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Abstract

Background: The ability to mobilize CD34+ cells is well established in a variety of clinical contexts but has not been extensively studied in the chronic myocardial ischemia (CMI) population. We examined the patterns and factors influencing mobilization of CD34+ cells in CMI subjects as well as the impact of cell mobilization ability on total exercise time and angina frequency.

Methods: ACT34-CMI was a Phase 2 prospective, randomized, double-blind, placebo controlled study to evaluate the safety and efficacy of 2 doses of selected autologous-CD34+ cells administered via targeted intramyocardial delivery in refractory angina patients (N=167). Subjects were mobilized with subcutaneous injections of G-CSF (5 mcg/kg/day for 5 days). Circulating CD34+ cell levels were measured using flow cytometry on Days 4 and 5. A single apheresis procedure was performed on Day 5. Analyses of clinical parameters were performed to identify characteristics associated with the ability to mobilize CD34+ cells. The relationship between the ability to mobilize cells (CD34+ cell count on Day 5) and efficacy outcomes was assessed.

Results: Increasing age (p=0.001) had the strongest negative association with mobilization. Non-smokers mobilized better than smokers (p=0.024). Females tended to mobilize better than males (p=0.022). There was a positive association between increasing BMI and mobilization (p=0.024). Higher platelet counts at baseline also correlated with better mobilization (p=0.005). Insulin dependent diabetics mobilized better than non-insulin dependent diabetics, which in turn mobilized better than non-diabetics (p=0.028). History of hypertension, MI, CHF, tachycardia, pericardial effusion or pacemaker was not significantly associated with ability to mobilize CD34+ cells. The ability to mobilize CD34+ cells did not appear to impact changes in angina frequency or change from baseline in total exercise time during the follow-up period.

Conclusions: While the ability to mobilize CD34+ cells is influenced by the clinical parameters identified, both good and poor mobilizers appear to respond similarly in terms of improvements in angina frequency and change from baseline in total exercise time following intramyocardial delivery of Auto-CD34+ cells.